tbuckley/cabot-search huggingface dataset:
A Multifunctional Hydrogel for Simultaneous Visible H<sub>2</sub>O<sub>2</sub> Monitoring And Accelerating Diabetic Wound Healing
Authors: Jimin Huang, Yi Zheng, Huicong Niu, Jinzhou Huang, XinXin Zhang, Jiajie Chen, Bing Ma, Chengtie Wu, Yi Cao, Yufang Zhu
Journal: Advanced Healthcare Materials (2023)

Diabetic wound is one of the chronic wounds that is difficult to heal, and effective treatment of it still confronts a great challenge. Monitoring the variation of diabetic wound microenvironment (such as hydrogen peroxide (H
Prediabetic HbA1c and Cortical Atrophy: Underlying Neurobiology
Authors: Jean Shin, Yash Patel, Nadine Parker, Tomas Paus, Zdenka Pausova
Journal: Diabetes Care (2023)

OBJECTIVE To investigate the relationship between blood glycated hemoglobin (HbA1c) and cerebral cortical thickness (CT) and identify potential cellular mechanisms involved. RESEARCH DESIGN AND METHODS A cohort of 30,579 adults age 45 to 81 (mean ± SD: 64 ± 7.5) years with available data on brain MRI and blood HbA1c levels was analyzed. The relationship between HbA1c and CT was probed using independent spatial profiles of cell-specific gene expression. Lastly, a genome-wide association study was conducted on the shared variance between HbA1c and CT. RESULTS The HbA1c–CT association was noncontinuous, emerging negatively within the prediabetic range (39.6 mmol/mol). This association was strongest in brain regions with higher expression of genes specific to excitatory neurons and lower expression of genes specific to astrocytes and microglia. A significant locus implicated mitochondrial maintenance and ATP generation. CONCLUSIONS Effective glycemia control at prediabetic levels is warranted to preserve brain health and prevent prediabetes-related neurobiologic perturbations.
Ibrutinib-based therapy reinvigorates CD8+ T cells compared to chemoimmunotherapy: immune monitoring from the E1912 trial
Authors: Despoina Papazoglou, Xin Victoria Wang, Tait D. Shanafelt, Connie E. Lesnick, Nikolaos Ioannou, Giulia De Rossi, Sylvia Herter, Marina Bacac, Christian Klein, Martin S. Tallman, Neil E. Kay, Alan G. Ramsay
Journal: Blood (2023)

Bruton tyrosine kinase inhibitors (BTKis) that target B-cell receptor signaling have led to a paradigm shift in chronic lymphocytic leukemia (CLL) treatment. BTKis have been shown to reduce abnormally high CLL-associated T-cell counts and the expression of immune checkpoint receptors concomitantly with tumor reduction. However, the impact of BTKi therapy on T-cell function has not been fully characterized. Here, we performed longitudinal immunophenotypic and functional analysis of pretreatment and on-treatment (6 and 12 months) peripheral blood samples from patients in the phase 3 E1912 trial comparing ibrutinib-rituximab with fludarabine, cyclophosphamide, and rituximab (FCR). Intriguingly, we report that despite reduced overall T-cell counts; higher numbers of T cells, including effector CD8+ subsets at baseline and at the 6-month time point, associated with no infections; and favorable progression-free survival in the ibrutinib-rituximab arm. Assays demonstrated enhanced anti-CLL T-cell killing function during ibrutinib-rituximab treatment, including a switch from predominantly CD4+ T-cell:CLL immune synapses at baseline to increased CD8+ lytic synapses on-therapy. Conversely, in the FCR arm, higher T-cell numbers correlated with adverse clinical responses and showed no functional improvement. We further demonstrate the potential of exploiting rejuvenated T-cell cytotoxicity during ibrutinib-rituximab treatment, using the bispecific antibody glofitamab, supporting combination immunotherapy approaches.
Health-Related Quality of Life in Patients With Metastatic Colorectal Cancer Undergoing Systemic Therapy With or Without Maximal Tumor Debulking
Authors: Lotte Bakkerus, Laurien M. Buffart, Tineke E. Buffart, Yannick M. Meyer, Barbara M. Zonderhuis, Cornelis J.A. Haasbeek, Kathelijn S. Versteeg, Olaf J.L. Loosveld, Jan Willem B. de Groot, Mathijs P. Hendriks, Cornelis Verhoef, Hendrik M.W. Verheul, Elske C. Gootjes
Journal: Journal of the National Comprehensive Cancer Network (2023)

Maintaining a sufficient health-related quality of life (HRQoL) is important in the palliative treatment of patients with metastatic colorectal cancer (mCRC). The ORCHESTRA trial (ClinicalTrials.gov identifier: NCT01792934) is designed to prospectively evaluate overall survival benefit and impact on HRQoL of tumor debulking when added to first-line palliative systemic therapy in patients with multiorgan mCRC. In the present study, we report the HRQoL associated with this combination treatment compared with standard systemic therapy.Patients included in the ORCHESTRA trial with clinical benefit after 3 or 4 cycles of first-line palliative systemic therapy with fluoropyrimidines and oxaliplatin with or without bevacizumab were randomly assigned to maximal tumor debulking followed by systemic therapy versus systemic therapy alone. Patients completed the EORTC Quality of Life Questionnaire-Core 30 and the Multidimensional Fatigue Inventory questionnaire at prespecified time points during treatment. Between-group differences in HRQoL over time were evaluated with linear mixed model analyses. A pattern mixture approach was applied to correct for missing questionnaires due to progressive disease.A total of 300 patients were randomized to the intervention arm (n=148) or the standard arm (n=152). No statistically significant or clinically relevant differences in HRQoL and fatigue were observed when tumor debulking was added to systemic therapy. In patients of both study arms, HRQoL after 1 year of treatment was not significantly different from HRQoL at the time of randomization. Patients in the intervention arm experienced serious adverse events (SAEs) twice as often as patients in the standard arm (P≤.001).Maximal tumor debulking in combination with palliative systemic therapy in patients with multiorgan mCRC was significantly associated with more SAEs resulting from local therapy but no difference in HRQoL compared with palliative systemic therapy alone. There is a remarkable lack of association between the occurrence of SAEs and impact on HRQoL.
A real-time deep learning-based system for colorectal polyp size estimation by white-light endoscopy: development and multicenter prospective validation
Authors: Jing Wang, Ying Li, Shuyu Li, Honggang Yu, Boru Chen, Du Cheng, Fei Liao, Tao Tan, Qinghong Xu, Zhifeng Liu, Yuan Huang, Ci Zhu, Wenbing Cao, Liwen Yao, Zhifeng Wu, Lianlian Wu, Chenxia Zhang, Bing Xiao, Ming Xu, Jun Liu
Journal: Endoscopy (2023)

Abstract Background The choice of polypectomy device and surveillance intervals for colorectal polyps are primarily decided by polyp size. We developed a deep learning-based system (ENDOANGEL-CPS) to estimate colorectal polyp size in real time. Methods ENDOANGEL-CPS calculates polyp size by estimating the distance from the endoscope lens to the polyp using the parameters of the lens. The depth estimator network was developed on 7297 images from five virtually produced colon videos and tested on 730 images from seven virtual colon videos. The performance of the system was first evaluated in nine videos of a simulated colon with polyps attached, then tested in 157 real-world prospective videos from three hospitals, with the outcomes compared with that of nine endoscopists over 69 videos. Inappropriate surveillance recommendations caused by incorrect estimation of polyp size were also analyzed. Results The relative error of depth estimation was 11.3% (SD 6.0%) in successive virtual colon images. The concordance correlation coefficients (CCCs) between system estimation and ground truth were 0.89 and 0.93 in images of a simulated colon and multicenter videos of 157 polyps. The mean CCC of ENDOANGEL-CPS surpassed all endoscopists (0.89 vs. 0.41 [SD 0.29]; P&lt;0.001). The relative accuracy of ENDOANGEL-CPS was significantly higher than that of endoscopists (89.9% vs. 54.7%; P&lt;0.001). Regarding inappropriate surveillance recommendations, the system's error rate is also lower than that of endoscopists (1.5% vs. 16.6%; P&lt;0.001). Conclusions ENDOANGEL-CPS could potentially improve the accuracy of colorectal polyp size measurements and size-based surveillance intervals.
An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma
Authors: Ross Firestone, Alexander M. Lesokhin, Saad Z. Usmani
Journal: Blood Cancer Discovery (2023)

Summary: In the past year, three new bispecific antibodies have received accelerated FDA approval for the treatment of relapsed/refractory multiple myeloma. In this article, we review the available data for these three agents, teclistamab, elranatamab, and talquetamab, and discuss practical considerations for their use in clinical settings while the medical community awaits randomized phase III clinical trial datasets comparing them to standard-of-care regimens.
Erratum
Authors: Daan Lanser, Anne-Marie Dingemans, Ron Mathijssen, G Marijn Veerman
Journal: Journal of the National Comprehensive Cancer Network (2023)

we are currently conducting a follow-up study to assess the safe coadministration of semaglutide, a glucagon-like peptide 1 receptor agonist, alongside alectinib. 4Given that clinical relevant weight gain is a common side effect of alectinib, this popular new drug might present a potential solution or prevention for weight gain. 5Should our new study reveal no drug-drug interactions, there is no reason to anticipate negative effects of semaglutide on alectinib treatment from a pharmacological perspective.
Effects of oral anticoagulation in people with atrial fibrillation after spontaneous intracranial haemorrhage (COCROACH): prospective, individual participant data meta-analysis of randomised trials
Authors: Rustam Al-Shahi Salman, Jacqueline Stephen, Jayne F Tierney, Steff C Lewis, David E Newby, Adrian R Parry-Jones, Philip M White, Stuart J Connolly, Oscar R Benavente, Dar Dowlatshahi, Charlotte Cordonnier, Catherine M Viscoli, Kevin N Sheth, Hooman Kamel, Roland Veltkamp, Kristin T Larsen, Jeannette Hofmeijer, Henk Kerkhoff, Floris H B M Schreuder, Ashkan Shoamanesh, Catharina J M Klijn, H Bart van der Worp, Didier Klug, Barbara Casolla, Laurent Puy, Morgane Coffee, Grégory Kuchcinski, Julien Labreuche, Koen M. van Nieuwenhuizen, Ale Algra, Isabelle C. van Gelder, L. Jaap Kappelle, Gabriel J.E. Rinkel, Roger E.G. Schutgens, Pooja Khatri, Robin Conwit, Guido Falcone, Jordan Elm, Craig S. Anderson, Lili Song, Jeyaraj Pandian, Robert G. Hart, Mukul Sharma, Hany Aref, Wadea Tarhuni, Joan Marti Fabregas, Hans-Christoph Diener, Matthias Endres, Robin Lemmens, Sun U. Kwon, Byung-Chul Lee, Sebastian Ameriso, Truman J. Milling, Scott E. Kasner, Robert Mikulik, Denis Xavier, Ronny Beer, Danilo Toni, Jens Eckstein, David Seiffge, Jose M. Ferro, Georgios Tsivgoulis, Sanjib K. Sharma, Chia Wei-Liou, Stefan H. Hohnloser, Aristeidis Katsanos, Jackie Bosch, Jeff Healey, John Eikelboom, Alexander Khaw, David Gladstone, Aleksandra Pikula, Shelagh Coutts, Eric E. Smith, Ken Butcher, Thalia Field, Laura Gioia, Christian Stapf, Omid Halse, Peter Ringleb, Christian Enzinger, Igor Sibon, Joan Montaner, Valeria Caso, Peter Heuschmann, Gregory Y.H. Lip, Walter Haefeli, Stefanie Debette, Martin S. Dennis, Torgeir Bruun Wyller, Ole M. Rønning, Helle Eilertsen, Hege Ihle-Hansen, Else Charlotte Sandset, Johanna Pennlert, Eva-Lotta Glader, Christina Kruuse, Per Wester, Maria Carlsson, Elisabeth Forfang
Journal: The Lancet Neurology (2023)

The safety and efficacy of oral anticoagulation for prevention of major adverse cardiovascular events in people with atrial fibrillation and spontaneous intracranial haemorrhage are uncertain. We planned to estimate the effects of starting versus avoiding oral anticoagulation in people with spontaneous intracranial haemorrhage and atrial fibrillation.
Potent Personalized Venetoclax Partners for Acute Myeloid Leukemia Identified by <i>Ex Vivo</i> Drug Screening
Authors: Pamela S. Becker
Journal: Blood Cancer Discovery (2023)

Summary: High-throughput screens (HTS) have been utilized to assess the efficacy of single drugs against patient tumor samples with the purpose of optimizing precision therapy, but testing the synergy of drug combinations can identify the ideal second drug to add. With novel sophisticated HTS, effective venetoclax combinations can be revealed that provide the cell state, phenotype, and molecular features of the susceptible and resistant cell populations. See related article by Eide, Kurtz et al., p. 452 (14) .
A Randomized Trial of Closed-Loop Insulin Delivery Postpartum in Type 1 Diabetes
Authors: Lois E. Donovan, Denice S. Feig, Patricia Lemieux, Helen R. Murphy, Rhonda C. Bell, Ronald J. Sigal, Josephine Ho, Heidi Virtanen, Susan Crawford, Jennifer M. Yamamoto
Journal: Diabetes Care (2023)

This study aimed to evaluate the efficacy of closed-loop insulin delivery postpartum.In this open-label, randomized controlled trial, postpartum individuals with type 1 diabetes were randomized to hybrid closed-loop insulin delivery with the MiniMed 670G/770G system in automode or sensor-augmented pump therapy in the first 12-weeks postpartum followed by a continuation phase with closed-loop insulin delivery for all until 24 weeks postpartum.Eighteen participants (mean ± SD age 32 ± 3.5 years, diabetes duration 22 ± 7.3 years, and early pregnancy HbA1c 52 ± 6.8 mmol/mol [6.9 ± 0.9%]) completed 24 weeks of postpartum follow-up. In the randomized phase, percent time in range 70-180 mg/dL (3.9-10 mmol/L) did not differ between groups (79.2 ± 8.7% vs. 78.2 ± 6.0%; P = 0.41). Participants randomized to closed-loop insulin delivery spent less time <70 mg/dL (3.9 mmol/L) and <54 mg/dL (3.0 mmol/L) (1.7 ± 0.8% vs. 5.5 ± 3.3% [P < 0.001] and 0.3 ± 0.2% vs. 1.1 ± 0.9% [P = 0.008]). Time >180 mg/dL (10 mmol/L) was not different between groups (18.7 ± 8.8% vs. 15.9 ± 7.7%; P = 0.21). In the continuation phase, those initially randomized to sensor-augmented pump therapy had less time <70 mg/dL after initiation of closed-loop insulin delivery (5.5 ± 3.3% vs. 3.3 ± 2.2%; P = 0.039). The closed-loop group maintained similar glycemic metrics in both study phases. There were no episodes of diabetic ketoacidosis or severe hypoglycemia in the randomized or continuation phase in either group.Women randomized to closed-loop insulin delivery postpartum had less hypoglycemia than those randomized to sensor-augmented pump therapy. There were no safety concerns. These findings are reassuring for use of closed-loop insulin delivery postpartum because of its potential to reduce hypoglycemia.
Critical Care Education and the ICU Care Continuum
Authors: Prateek Sehgal, Dominique Piquette, Michael Detsky, Nava Maham, Maria Jogova, David Hall, Hannah Wozniak, Margaret Herridge
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Critical Care Education and the ICU Care Continuum." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Letter to the Editor: Inclusive and Adequate Care Overcoming All Health Care Gaps: The Need to Specifically Look to the LGBTQI+ Population
Authors: Massimo De Martinis, Lia Ginaldi
Journal: Journal of the National Comprehensive Cancer Network (2023)

"Letter to the Editor: Inclusive and Adequate Care Overcoming All Health Care Gaps: The Need to Specifically Look to the LGBTQI+ Population" published on Oct 2023 by National Comprehensive Cancer Network.
Machine Learning–Based Early Warning Systems for Acute Care Utilization During Systemic Therapy for Cancer
Authors: Robert C. Grant, Jiang Chen He, Ferhana Khan, Ning Liu, Sho Podolsky, Yosuf Kaliwal, Melanie Powis, Faiyaz Notta, Kelvin K.W. Chan, Marzyeh Ghassemi, Steven Gallinger, Monika K. Krzyzanowska
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Emergency department visits and hospitalizations frequently occur during systemic therapy for cancer. We developed and evaluated a longitudinal warning system for acute care use. Methods: Using a retrospective population-based cohort of patients who started intravenous systemic therapy for nonhematologic cancers between July 1, 2014, and June 30, 2020, we randomly separated patients into cohorts for model training, hyperparameter tuning and model selection, and system testing. Predictive features included static features, such as demographics, cancer type, and treatment regimens, and dynamic features, such as patient-reported symptoms and laboratory values. The longitudinal warning system predicted the probability of acute care utilization within 30 days after each treatment session. Machine learning systems were developed in the training and tuning cohorts and evaluated in the testing cohort. Sensitivity analyses considered feature importance, other acute care endpoints, and performance within subgroups. Results: The cohort included 105,129 patients who received 1,216,385 treatment sessions. Acute care followed 182,444 (15.0%) treatments within 30 days. The ensemble model achieved an area under the receiver operating characteristic curve of 0.742 (95% CI, 0.739–0.745) and was well calibrated in the test cohort. Important predictive features included prior acute care use, treatment regimen, and laboratory tests. If the system was set to alarm approximately once every 15 treatments, 25.5% of acute care events would be preceded by an alarm, and 47.4% of patients would experience acute care after an alarm. The system underestimated risk for some treatment regimens and potentially underserved populations such as females and non-English speakers. Conclusions: Machine learning warning systems can detect patients at risk for acute care utilization, which can aid in preventive intervention and facilitate tailored treatment. Future research should address potential biases and prospectively evaluate impact after system deployment.
NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024
Authors: Mary B. Daly, Tuya Pal, Kara N. Maxwell, Jane Churpek, Wendy Kohlmann, Zahraa AlHilli, Banu Arun, Saundra S. Buys, Heather Cheng, Susan M. Domchek, Susan Friedman, Veda Giri, Michael Goggins, Andrea Hagemann, Ashley Hendrix, Mollie L. Hutton, Beth Y. Karlan, Nawal Kassem, Seema Khan, Katia Khoury, Allison W. Kurian, Christine Laronga, Julie S. Mak, John Mansour, Kevin McDonnell, Carolyn S. Menendez, Sofia D. Merajver, Barbara S. Norquist, Kenneth Offit, Dominique Rash, Gwen Reiser, Leigha Senter-Jamieson, Kristen Mahoney Shannon, Kala Visvanathan, Jeanna Welborn, Myra J. Wick, Marie Wood, Matthew B. Yurgelun, Mary A. Dwyer, Susan D. Darlow
Journal: Journal of the National Comprehensive Cancer Network (2023)

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1 , BRCA2 , CDH1 , PALB2 , PTEN , and TP53 , and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.
Validation of the PREDICT Prognostication Tool in US Patients With Breast Cancer
Authors: Nickolas Stabellini, Lifen Cao, Christopher W. Towe, Megan E. Miller, Artur H. Sousa-Santos, Amanda L. Amin, Alberto J. Montero
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: PREDICT is an online prognostication tool derived from breast cancer registry information on approximately 6,000 women treated in the United Kingdom that estimates the postsurgical treatment benefit of surgery alone, chemotherapy, trastuzumab, endocrine therapy, and/or adjuvant bisphosphonates in early-stage breast cancer. Our aim was to validate the PREDICT algorithm in predicting 5- and 10-year overall survival (OS) probabilities using real-world outcomes among US patients with breast cancer. Methods: A retrospective study was performed including women diagnosed with unilateral breast cancer in 2004 through 2012. Women with primary unilateral invasive breast cancer were included. Patients with bilateral or metastatic breast cancer, no breast surgery, or missing critical clinical information were excluded. Prognostic scores from PREDICT were calculated and external validity was approached by assessing statistical discrimination through area under time-dependent receiver-operator curves (AUC) and comparing the predicted survival to the observed OS in relevant subgroups. Results: We included 708,652 women, with a median age of 58 years. Most patients were White (85.4%), non-Hispanic (88.4%), and diagnosed with estrogen receptor–positive breast cancer (79.6%). Approximately 50% of patients received adjuvant chemotherapy, 67% received adjuvant endocrine therapy, 60% underwent a partial mastectomy, and 59% had 1 to 5 axillary sentinel nodes removed. Median follow-up time was 97.7 months. The population’s 5- and 10-year OS were 89.7% and 78.7%, respectively. Estimated 5- and 10-year median survival with PREDICT were 88.3% and 73.8%, and an AUC of 0.77 and 0.76, respectively. PREDICT performed most poorly in patients with high Charlson-Deyo comorbidity scores (2–3), where PREDICT overestimated OS. Sensitivity analysis by year of diagnosis and HER2 status showed similar results. Conclusions: In this prognostic study utilizing the National Cancer Database, the PREDICT tool accurately predicted 5- and 10-year OS in a contemporary and diverse population of US patients with nonmetastatic breast cancer.
Predictors of ≥15% Weight Reduction and Associated Changes in Cardiometabolic Risk Factors With Tirzepatide in Adults With Type 2 Diabetes in SURPASS 1–4
Authors: Maciej T. Małecki, Rachel L. Batterham, Naveed Sattar, Joshua A. Levine, Ángel Rodríguez, Brandon K. Bergman, Hui Wang, Gabriela Ghimpeteanu, Clare J. Lee
Journal: Diabetes Care (2023)

OBJECTIVE To identify predictors of body weight (BW) reduction of ≥15% with tirzepatide treatment and to describe associated clinical parameters of participants with type 2 diabetes (T2D) who achieved different categorical measures of BW reduction (&amp;lt;5%, ≥5 to &amp;lt;10%, ≥10 to &amp;lt;15%, and ≥15%) across four studies from the phase 3 SURPASS clinical trial program for T2D. RESEARCH DESIGN AND METHODS The multivariate model for predictor of a BW reduction of ≥15% included age, sex, race, BW, HbA1c, tirzepatide dose and baseline metformin use, fasting serum glucose, and non-HDL cholesterol. Baseline characteristics and change from baseline to week 40/42 for efficacy parameters were described and analyzed in treatment-adherent participants (≥75% doses administered and on treatment at week 40/42) receiving once weekly tirzepatide (5 mg, 10 mg, or 15 mg) (N = 3,188). RESULTS Factors significantly associated with achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, and lower HbA1c, fasting serum glucose, and non-HDL cholesterol at baseline. With higher categorical BW reduction, there were greater reductions in HbA1c, triglycerides, ALT, waist circumference, and blood pressure. CONCLUSIONS Baseline factors associated with a higher likelihood of achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, better glycemic status, and lower non-HDL cholesterol. With greater BW reduction, participants with T2D achieved larger improvements in glycemia and cardiometabolic risk parameters. These findings help inform which people with T2D are most likely to achieve greater BW reduction with improved cardiometabolic risk factors with tirzepatide.